Effects of dopamine depletion in the medial prefrontal cortex on the stress-induced increase in extracellular dopamine in the nucleus accumbens core and shell

doi:10.1016/S0306-4522(96)00421-6

Neuroscience

Volume 77, Issue 1, 6 January 1997, Pages 141-153

https://doi.org/10.1016/S0306-4522(96)00421-6 Get rights and content

Abstract

In the present study we examined whether depletion of dopamine in the medial prefrontal cortex alters the neurochemical activity of mesoaccumbens dopamine neurons and/or their behavioral correlate, motor behavior. Infusion of 6-hydroxydopamine (1 μg) into the medial prefrontal cortex of rats pretreated with a norepinephrine uptake blocker produced a 70% loss of tissue dopamine, with relative sparing of the norepinephrine content (−23%) in that region. Using in vivo microdialysis, we monitored basal and evoked extracellular dopamine in the nucleus accumbens core and shell of control and lesioned rats. The concentration of basal extracellular dopamine in the nucleus accumbens core was similar in control and lesioned rats; however, basal dopamine efflux in the nucleus accumbens shell was approximately 30% higher in lesioned rats than in controls. Lesions did not alter the ability of systemic d-amphetamine (1.5 mg/kg, i.p.) to increase extracellular dopamine in the nucleus accumbens shell. In contrast, the dopamine depletion in the medial prefrontal cortex attenuated the amphetamine-induced increase in extracellular dopamine in the nucleus accumbens core, as well as the amphetamine-induced increase in locomotor activity. Lesions did not significantly alter the effects of tail pressure (30 min) on extracellular dopamine in the nucleus accumbens core. However, the depletion of dopamine in the medial prefrontal cortex potentiated the stress-induced increase in extracellular dopamine in the nucleus accumbens shell. These data demonstrate that mesocortical dopamine neurons influence (i) amphetamine-induced dopamine efflux in the nucleus accumbens core and (ii) stress-evoked dopamine efflux in the nucleus accumbens shell.

It has been proposed that a disruption in the interaction between cortical and subcortical dopamine neurons is involved in the pathophysiology of schizophrenia. The present data raise the possibility that a disruption in the interaction between mesocortical dopamine neurons and dopamine neurons projecting to the nucleus accumbens shell is involved in those symptoms of schizophrenia that are influenced by stress.

Section snippets

Animals and materials

Male Sprague–Dawley rats (Zivic-Miller, Allison Park, PA, U.S.A.) were housed singly in wire mesh cages (20 cm×20 cm×30 cm) in a temperature-controlled room (22–23°C). Lights were on from 8.00 a.m. to 8.00 p.m. and lab chow and water were available ad libitum. Upon arrival, rats were allowed at least one week to acclimate to the colony room before any treatment. All treatments were performed during the light phase of the light/dark cycle. Procedures for treatment of rats were approved by the

Basal extracellular dopamine and 3,4-dihydroxyphenylacetic acid in the nucleus accumbens core and shell of control and lesioned rats

Post mortem analysis of tissue from the rats included in the microdialysis experiments confirmed that infusion of 1 μg 6-OHDA into the mPFC depleted tissue DA content (−70±4%), while largely sparing the NE concentration (−23±4%) in that region (t₃₁=6.61 and 4.05, respectively). The absolute concentrations of DA and NE in mPFC tissue of control rats were 0.10±0.01 and 0.22±0.01 ng/mg tissue wet weight, respectively. In control rats, the basal concentration of extracellular DA was significantly

Anatomical localization of microdialysis probes in the nucleus accumbens core and shell

A number of studies support the anatomical division of the NAS into its lateral and medial subregions, the core and shell, respectively. For example, there are differences in the distribution of various neurochemicals between the NAS subareas.38, 74, 76, 79In addition, the NAS core and shell differ in connectivity such that the core is aligned with neuronal circuits subserving motor function, whereas the shell is interconnected with the limbic system.6, 7, 33, 81Recent studies suggest that the

Conclusions

It has been proposed that there are two parallel cortico-accumbal-pallido-thalamocortical circuits that subserve limbic and motor functions.19, 22, 80As components of both the “motor” and “limbic” circuits, midbrain DA neurons provide input to cortical and subcortical brain regions. Our data support the view that a dysfunction in the modulatory capacity of DA in the cortex can alter the activity of DA neurons in subcortical areas. In addition, our data suggest that the interaction between

Acknowledgements

We gratefully acknowledge Dr Susan R. Sesack for training and supervision of the retrograde tracing, and Dr David A. Lewis and Mr Richard E. Whitehead for assistance with immunocytochemistry. We thank Dr Matthew Martin-Iverson for the use of his behavioral observation software for measuring stereotyped behavior. This work was supported by awards from the Tourette Syndrome Association, the Scottish Rite Schizophrenia Research Program, the National Alliance for Research on Schizophrenia and

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Effects of dopamine depletion in the medial prefrontal cortex on the stress-induced increase in extracellular dopamine in the nucleus accumbens core and shell

Abstract

Section snippets

Animals and materials

Basal extracellular dopamine and 3,4-dihydroxyphenylacetic acid in the nucleus accumbens core and shell of control and lesioned rats

Anatomical localization of microdialysis probes in the nucleus accumbens core and shell

Conclusions

Acknowledgements

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An excitant amino acid projection from the medial prefrontal cortex to the anterior part of nucleus accumbens in the rat

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Anatomical analysis of the involvement of the mesolimbocortical dopamine in the locomotor stimulant actions of d-amphetamine and apomorphine

Psychopharmacology